Overall survival (OS) was not significantly different between nivolumab (Opdivo) and chemotherapy with either gemcitabine (Gemzar) or pegylated liposomal doxorubicin in an open-label phase 3 clinical trial of patients with platinum-resistant ovarian cancer. Data from the NINJA trial, presented at the European Society for Medical Oncology Virtual Congress 2020 by Kohei Omatsu, MD, Head, Gynecologic Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, did show superior tolerability with nivolumab compared with chemotherapy and suggest a prolonged response in the nivolumab arm versus its comparators, despite a lower median progression-free survival (PFS).
NINJA is a multicenter, open-label, randomized phase 3 study comparing nivolumab versus gemcitabine or pegylated liposomal doxorubicin in 316 patients with advanced or recurrent platinum-resistant ovarian cancer who were not previously treated with gemcitabine or pegylated liposomal doxorubicin. Patients were randomized 1:1 to receive nivolumab 240 mg intravenously every 2 weeks or to chemotherapy chosen by the investigator, either gemcitabine or pegylated liposomal doxorubicin.
Treatment was continued until disease progression or toxicity leading to discontinuation. The primary end point was OS.
More than three-fourths (77.8%) of study participants were treated with ≥2 chemotherapies prior to enrollment. The primary tumor site was the ovary in approximately 80% of patients.
The median OS in the nivolumab arm was 10.12 months versus 12.09 months in the chemotherapy arm, a nonsignificant difference (hazard ratio [HR], 1.03; 95% confidence interval [CI], 0.80-1.32; P = .808). The HR for OS was consistent in patients with programmed death-ligand 1 (PD-L1)-positive and PD-L1–negative tumors. Subgroup analysis showed a numerically longer OS with nivolumab in the 67 patients with clear-cell carcinoma (HR, 0.8; 95% CI, 0.5-1.3).
Median PFS was 2.04 months in the nivolumab arm versus 3.84 months in the chemotherapy arm (HR, 1.46; 95% CI, 1.15-1.85; P = .002).
The response rate was not significantly different between the 2 treatment arms—8% in the nivolumab group versus 13% in the arm randomized to either gemcitabine or pegylated liposomal doxorubicin (odds ratio, 0.6; 95% CI, 1.02-1.3; P = .191). Among the patients who responded, the median duration of overall response was longer for the 9 responders in the nivolumab group (18.7 months) compared with the 15 responders in chemotherapy group (7.4 months).
No new safety signals for nivolumab were observed in this trial, and nivolumab was well-tolerated compared with gemcitabine or pegylated liposomal doxorubicin. The rate of treatment-emergent grade 3/4 adverse events (AEs) was far lower in the nivolumab arm compared with the chemotherapy arm (22.4% vs 68.4%), as was the rate of all-grade AEs (62% vs 98%, respectively). In the nivolumab arm, the most common major AEs (all grades) were rash (10%), fatigue (9%), nausea (6%), diarrhea (6%), and pruritus (6%).
Study investigators are completing additional analyses to better understand the prolonged treatment response observed with nivolumab.